The Role of Gut Microbiota on Idiopathic Pulmonary Fibrosis Mediated by Circulating Inflammatory Proteins: A Two-Step, Two-Sample Mendelian Randomization Study

IF 2.3 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal Pub Date : 2025-09-09 DOI:10.1111/crj.70120

Hongyu Zhu, Caihua Chen, Haixie Guo, Bo Zhang, Quanteng Hu

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引用次数: 0

Abstract

Background

Persistent inflammation is a crucial characteristic of idiopathic pulmonary fibrosis (IPF). Gut microbiota (GM) contribute to the occurrence and development of several pulmonary diseases through the “gut–lung axis.” The genetic role of GM in IPF and the mediating effect of circulating inflammatory proteins.

Methods

A single nucleotide polymorphism (SNP) was used as an instrumental variable (IV) for exposure to evaluate the causal relationship between exposure and outcome. A two-step, two-sample Mendelian randomization study mainly based on an “inverse variance weighted (IVW)” approach was performed to explore the causal relationship between GM and IPF mediated by circulating inflammatory proteins.

Results

The IVW way illustrated 12 taxa (Bacillales, Gastranaerophilales, Selenomonadales, Family XIII, Bacteroidaceae, Bacteroides, and Actinomyces, Bifidobacterium, Oscillibacter, Ruminococcus gnavus, Subdoligranulum, Veillonella) of GM and 8 circulating inflammatory proteins (CCL11, CXCL6, CXCL9, CCL8, CCL7, NRTN, STAMPB, and TGFa) had suggestive evidence of causality on IPF. The mediation MR demonstrated the causal pathway from Actinomyces to IPF was partly mediated by CCL11 (the mediation effect: 0.063, 95% CI [1.016–1.126]; p = 0.004) with a mediation proportion of 13.035%.

Conclusions

These findings may suggest a genetically predicted association between GM and IPF mediated by circulating inflammatory proteins.

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肠道菌群在循环炎性蛋白介导的特发性肺纤维化中的作用：一项两步、两样本孟德尔随机研究

背景持续炎症是特发性肺纤维化（IPF）的一个重要特征。肠道微生物群（GM）通过“肠-肺轴”促进几种肺部疾病的发生和发展。转基因在IPF中的遗传作用及循环炎症蛋白的介导作用。方法采用单核苷酸多态性（SNP）作为暴露的工具变量（IV），评价暴露与预后的因果关系。一项主要基于“逆方差加权（IVW）”方法的两步、两样本孟德尔随机化研究，旨在探讨GM与循环炎症蛋白介导的IPF之间的因果关系。结果IVW方法显示12个类群（芽胞杆菌、嗜气胃杆菌、单胞硒门、13科、拟杆菌科、拟杆菌科、放线菌科、双歧杆菌、Oscillibacter、瘤胃球菌、小肠子菌、小肠子菌）的GM和8个循环炎性蛋白（CCL11、CXCL6、CXCL9、CCL8、CCL7、NRTN、STAMPB、TGFa）与IPF存在因果关系。中介MR表明CCL11部分介导了放线菌与IPF的因果通路（中介效应：0.063,95% CI [1.016-1.126]; p = 0.004），中介比例为13.035%。结论：这些发现可能表明GM和循环炎症蛋白介导的IPF之间存在遗传预测关联。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Respiratory Journal 医学-呼吸系统

CiteScore

3.70

自引率

0.00%

发文量

104

审稿时长

>12 weeks

期刊介绍： Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)